Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → cis-2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclopentanecarboxylic acid methylamide

HRID 1040859Notes

Reaction equation

HRID 1040859 reaction equation
[CH3:1][NH:2][C:3]([C@@H:5]1[CH2:9][CH2:8][CH2:7][C@@H:6]1[NH:10][C:11]1[C:16]([Cl:17])=[CH:15][N:14]=[C:13](Cl)[N:12]=1)=[O:4].[CH3:19][O:20][CH2:21][CH2:22][N:23]1[CH2:29][CH2:28][C:27]2[CH:30]=[C:31]([NH2:34])[CH:32]=[CH:33][C:26]=2[CH2:25][CH2:24]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(O)(C)C>[CH3:1][NH:2][C:3]([C@@H:5]1[CH2:9][CH2:8][CH2:7][C@@H:6]1[NH:10][C:11]1[C:16]([Cl:17])=[CH:15][N:14]=[C:13]([NH:34][C:31]2[CH:32]=[CH:33][C:26]3[CH2:25][CH2:24][N:23]([CH2:22][CH2:21][O:20][CH3:19])[CH2:29][CH2:28][C:27]=3[CH:30]=2)[N:12]=1)=[O:4]

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 574160893-(2-Methoxyethyl)-2,3,4,5-tetrahydro-1h-3-benzazepin-7-amineHCID 86633889cis-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclopentanecarboxylic acid methylamide

Product 1

HCID 66829873cis-2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclopentanecarboxylic acid methylamideYield 53%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

cis-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclopentanecarboxylic acid methylamide (60 mg, 0.208 mmol), 3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (46 mg, 0.208 mmol) and camphorsulfonic acid (72 mg, 0.312 mmol) were combined in 2 mL isopropanol and heated at 120° C. in microwave for a total of 75 min. The reaction was concentrated to be taken up in dichloromethane and washed with saturated sodium bicarbonate solution (2×30 mL). The organic layer was dried over MgSO4 and filtered. The filtrate was chromatographed on an ISCO flash column from 0-100% ethyl acetate in hexanes. The product was collected as a foam after concentrating to afford 52 mg (53%) of a white foam. Compound 2: mp 176° C.; MS (ES+ calculated—472; found—473 M+H). 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H), 7.39 (s, 1H), 7.30 (s, 1H), 7.17 (s, 1H), 7.03 (d, J=8 Hz, 1H), 6.21 (d, J=7, 1H), 5.52 (br s, 1H), 4.58 (t, J=7 Hz, 1H), 3.55 (t, J=5, 2H), 3.34 (s, 3H), 2.91 (br s, 6H), 2.75 (m, 4H), 2.72 (m, 4H), 2.15 (m, 2H), 1.96 (m, 4H), 1.64 (m, 1H) ppm.

Workup

  1. concentrationThe reaction was concentrated
  2. washwashed with saturated sodium bicarbonate solution (2×30 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customThe filtrate was chromatographed on an ISCO flash column from 0-100% ethyl acetate in hexanes
  6. customThe product was collected as a foam
  7. concentrationafter concentrating

Sources & evidence

ORD record
ord-7c89ec6984884b30a3727ff63dc88b42
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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